AR035626A1 - INHIBITORS OF INHIBITORS OF THYROSINE KINASE, PHARMACEUTICAL COMPOSITION, PROCEDURE TO PREPARE IT, AND, USE OF THE COMPOUNDS IN THE PREPARATION OF MEDICINES - Google Patents

INHIBITORS OF INHIBITORS OF THYROSINE KINASE, PHARMACEUTICAL COMPOSITION, PROCEDURE TO PREPARE IT, AND, USE OF THE COMPOUNDS IN THE PREPARATION OF MEDICINES

Info

Publication number
AR035626A1
AR035626A1 ARP000105472A ARP000105472A AR035626A1 AR 035626 A1 AR035626 A1 AR 035626A1 AR P000105472 A ARP000105472 A AR P000105472A AR P000105472 A ARP000105472 A AR P000105472A AR 035626 A1 AR035626 A1 AR 035626A1
Authority
AR
Argentina
Prior art keywords
alkyl
aob
aryl
cycloalkyl
heterocyclyl
Prior art date
Application number
ARP000105472A
Other languages
Spanish (es)
Original Assignee
Merck & Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck & Co Inc filed Critical Merck & Co Inc
Publication of AR035626A1 publication Critical patent/AR035626A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Obesity (AREA)
  • Vascular Medicine (AREA)
  • Psychiatry (AREA)
  • Communicable Diseases (AREA)
  • Endocrinology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Emergency Medicine (AREA)
  • Oncology (AREA)

Abstract

Se refieren compuestos de indol de fórmula (1) que inhiben, regulan y/o modulan la transducción de senales de tirosina quinasa, las composiciones que contienen estos compuestos, y los métodos de uso de los mismos para tratar enfermedades y condiciones que dependen de tirosina quinasa, tales como angiogénesis, cáncer, desarrollo de tumores, arteriosclerosis, degeneración macular relacionada con la edad, retinopatía diabética, enfermedades inflamatorias, y similares en mamíferos. Reivindicación 1: Un compuesto de indol caracterizado porque es de fórmula (1) o una sal farmacéuticamente aceptable o un estereoisómero del mismo, donde Z es fórmulas (2) o (3) o (4); W1 es S, O o N-R; V1 es N o C; W2 es N o C; V2 es S, O o N-R; a es 0 o 1; b es 0 o 1; m es 0, 1 o 2; s es 1 o 2; t es 1, 2 o 3; X=Y es C=N, N=C, o C=C; R es H o alquilo C1-6; R1 y R5 están independientemente seleccionados de: H, (C=O)aOb alquilo C1-10, (C=O)aOb arilo, (C=O)aOb alquenilo C2-10, (C=O)aOb alquinilo C2-10, CO2H, halo, OH, Ob perfluoroalquilo C1-6, (C=O)a NR7R8, CN, (C=O)aOb cicloalquilo C3-8, y (C=O)aOb heterociclilo, dicho alquilo, arilo, alquenilo, alquinilo cicloalquilo y heterociclilo está opcionalmente sustituido con uno o más sustituyentes seleccionados de R6; R2 y R3 están independientemente seleccionados de: H, (C=O)Oa alquilo C1-6, (C=O)Oa arilo, alquilo C1-6, SO2Ra, y arilo; R4 está seleccionado de: (C=O)aOb alquilo C1-10, (C=O)aOb arilo, (C=O)aOb alquenilo C2-10, (C=O)aOb alquinilo C2-10, CO2H, halo, OH, Ob perfluoralquilo C1-6, (C=O)a NR7R8, CN, (C=O)aOb cicloalquilo C3-8, y (C=O)aOb heterociclilo, dicho alquilo, arilo, alquenilo, alquinilo, cicloalquilo y heterociclilo está opcionalmente sustituido con uno o más sustituyentes seleccionados de R6; R6 es(C=O)aOb alquilo C1-6, (C=O)aOb arilo, alquenilo C2-10, alquinilo C2-10, (C=O)aOb heterociclilo, CO2H, halo, CN, OH, Ob perfluoralquilo C1-3, Oa(C=O)b NR7R8, oxo, CHO, (N=O)R7R8, o (C=O)aOb cicloalquilo C3-8, dicho alquilo, arilo, alquenilo, alquinilo, heterociclilo y cicloalquilo está opcionalmente sustituido con uno o más sustituyentes seleccionados de R6a; R6a está seleccionado de: C=O)rOs alquilo C1-10, donde r y s son independientemente 0 o 1, Or perfluoralquilo C1-3, donde r es 0 o 1, alquileno C0-6-S(O)mRa, donde m es 0, 1 o 2, oxo, OH, halo, CN, alquenilo C2-10, alquinilo C2-10, cicloalquilo C3-6, alquileno C0-6-arilo, alquileno C0-6-heterociclilo, alquileno C0-6-N(Rb)2, C(O)Ra, alquileno C0-6-CO2Ra, C(O)H, y alquileno C0-6-CO2H, dicho alquilo, alquenilo, alquinilo, cicloalquilo, arilo y heterociclilo está opcionalmente sustituido con hasta tres sustituyentes seleccionados de Rb, OH, alcoxi C1-6, halógeno, CO2H, CN, O(C=O) alquilo C1-6, oxo, y N(Rb)2; R7 y R8 están independientemente seleccionados de: H, (C=O)Ob alquilo C1-10, (C=O)Ob cicloalquilo C3-8, (C=O)Ob arilo, (C=O)Ob heterociclilo, alquilo C1-10, arilo, alquenilo C2-10, alquinilo C2-10, heterociclilo, cicloalquilo C3-8, SO2Ra, y (C=O)NRb 2, dicho alquilo, cicloalquilo, arilo, heterociclilo, alquenilo y alquinilo están opcionalmente sustituidos con uno o más sustituyentes seleccionados de R6a, o R7 y R8 pueden estar tomados conjuntamente al nitrógeno al cual están unidos para formar un heterociclo monocíclico o bicíclico con 5-7 miembros en cada anillo y que contiene opcionalmente además del nitrógeno uno o dos heteroátomos adicionales seleccionados de N, O y S, estando dicho heterociclo monocíclico o bicíclico opcionalmente sustituido con uno o más sustituyentes seleccionados de R6a; Ra es alquilo C1-6, cicloalquilo C3-6, arilo, o heterociclilo; y Rb es H, alquilo C1-6, arilo, heterociclilo, cicloalquilo C3-6, (C=O)O alquilo c1-6, (C=O) alquilo C1-6 o S(O)2Ra.Indole compounds of formula (1) which inhibit, regulate and / or modulate the transduction of tyrosine kinase signals, the compositions containing these compounds, and the methods of using them to treat diseases and conditions that depend on tyrosine are referred to kinase, such as angiogenesis, cancer, tumor development, arteriosclerosis, age-related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals. Claim 1: An indole compound characterized in that it is of formula (1) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Z is formulas (2) or (3) or (4); W1 is S, O or N-R; V1 is N or C; W2 is N or C; V2 is S, O or N-R; a is 0 or 1; b is 0 or 1; m is 0, 1 or 2; s is 1 or 2; t is 1, 2 or 3; X = Y is C = N, N = C, or C = C; R is H or C1-6 alkyl; R1 and R5 are independently selected from: H, (C = O) aOb C1-10 alkyl, (C = O) aOb aryl, (C = O) aOb C2-10 alkenyl, (C = O) aOb C2-10 alkynyl , CO2H, halo, OH, Ob perfluoroalkyl C1-6, (C = O) to NR7R8, CN, (C = O) aOb C3-8 cycloalkyl, and (C = O) aOb heterocyclyl, said alkyl, aryl, alkenyl, alkynyl cycloalkyl and heterocyclyl is optionally substituted with one or more substituents selected from R6; R2 and R3 are independently selected from: H, (C = O) Oa C1-6 alkyl, (C = O) Oa aryl, C1-6 alkyl, SO2Ra, and aryl; R4 is selected from: (C = O) aOb C1-10 alkyl, (C = O) aOb aryl, (C = O) aOb C2-10 alkenyl, (C = O) aOb C2-10 alkynyl, CO2H, halo, OH, C1-6 perfluoralkyl Ob, (C = O) to NR7R8, CN, (C = O) a C3-8 cycloalkyl, and (C = O) aOb heterocyclyl, said alkyl, aryl, alkenyl, alkynyl, cycloalkyl and heterocyclyl is optionally substituted with one or more substituents selected from R6; R6 is (C = O) aOb C1-6 alkyl, (C = O) aOb aryl, C2-10 alkenyl, C2-10 alkynyl, (C = O) aOb heterocyclyl, CO2H, halo, CN, OH, Ob perfluoralkyl C1 -3, Oa (C = O) b NR7R8, oxo, CHO, (N = O) R7R8, or (C = O) aOb C3-8 cycloalkyl, said alkyl, aryl, alkenyl, alkynyl, heterocyclyl and cycloalkyl is optionally substituted with one or more substituents selected from R6a; R6a is selected from: C = O) rOs C1-10 alkyl, where rys are independently 0 or 1, Or perfluoralkyl C1-3, where r is 0 or 1, C0-6-S alkylene (O) mRa, where m is 0, 1 or 2, oxo, OH, halo, CN, C2-10 alkenyl, C2-10 alkynyl, C3-6 cycloalkyl, C0-6-aryl alkylene, C0-6-heterocyclyl alkylene, C0-6-N alkylene ( Rb) 2, C (O) Ra, C0-6-CO2 alkylene, C (O) H, and C0-6-CO2H alkylene, said alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl is optionally substituted with up to three substituents selected from Rb, OH, C1-6 alkoxy, halogen, CO2H, CN, O (C = O) C1-6 alkyl, oxo, and N (Rb) 2; R7 and R8 are independently selected from: H, (C = O) Ob C1-10 alkyl, (C = O) Ob C3-8 cycloalkyl, (C = O) Ob aryl, (C = O) Heterocyclyl ob, C1 alkyl -10, aryl, C2-10 alkenyl, C2-10 alkynyl, heterocyclyl, C3-8 cycloalkyl, SO2Ra, and (C = O) NRb 2, said alkyl, cycloalkyl, aryl, heterocyclyl, alkenyl and alkynyl are optionally substituted with one or more substituents selected from R6a, or R7 and R8 may be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing in addition to nitrogen one or two additional heteroatoms selected from N, O and S, said monocyclic or bicyclic heterocycle being optionally substituted with one or more substituents selected from R6a; Ra is C1-6 alkyl, C3-6 cycloalkyl, aryl, or heterocyclyl; and Rb is H, C1-6 alkyl, aryl, heterocyclyl, C3-6 cycloalkyl, (C = O) OR C1-6 alkyl, (C = O) C1-6 alkyl or S (O) 2Ra.

ARP000105472A 1999-10-19 2000-10-18 INHIBITORS OF INHIBITORS OF THYROSINE KINASE, PHARMACEUTICAL COMPOSITION, PROCEDURE TO PREPARE IT, AND, USE OF THE COMPOUNDS IN THE PREPARATION OF MEDICINES AR035626A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US16035699P 1999-10-19 1999-10-19

Publications (1)

Publication Number Publication Date
AR035626A1 true AR035626A1 (en) 2004-06-23

Family

ID=22576544

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP000105472A AR035626A1 (en) 1999-10-19 2000-10-18 INHIBITORS OF INHIBITORS OF THYROSINE KINASE, PHARMACEUTICAL COMPOSITION, PROCEDURE TO PREPARE IT, AND, USE OF THE COMPOUNDS IN THE PREPARATION OF MEDICINES

Country Status (40)

Country Link
US (1) US6306874B1 (en)
EP (1) EP1226136B1 (en)
JP (2) JP3822494B2 (en)
KR (1) KR100681724B1 (en)
CN (1) CN1213045C (en)
AR (1) AR035626A1 (en)
AT (1) ATE286045T1 (en)
AU (1) AU778588B2 (en)
BG (1) BG65585B1 (en)
BR (1) BR0014843A (en)
CA (1) CA2387351C (en)
CO (1) CO5261601A1 (en)
CZ (1) CZ20021390A3 (en)
DE (1) DE60017179T2 (en)
DZ (1) DZ3223A1 (en)
EA (1) EA005812B1 (en)
EE (1) EE05107B1 (en)
EG (1) EG24381A (en)
ES (1) ES2234698T3 (en)
GE (1) GEP20053530B (en)
HK (1) HK1054931A1 (en)
HR (1) HRP20020349A2 (en)
HU (1) HUP0203323A3 (en)
IL (2) IL148891A0 (en)
IS (1) IS2165B (en)
MX (1) MXPA02003887A (en)
MY (1) MY137656A (en)
NO (1) NO325696B1 (en)
NZ (1) NZ518001A (en)
PE (1) PE20010749A1 (en)
PL (1) PL202842B1 (en)
PT (1) PT1226136E (en)
RS (1) RS50380B (en)
SA (2) SA06270148B1 (en)
SK (1) SK286628B6 (en)
TR (1) TR200201051T2 (en)
TW (1) TWI239957B (en)
UA (1) UA74560C2 (en)
WO (1) WO2001029025A2 (en)
ZA (1) ZA200202985B (en)

Families Citing this family (172)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6846799B1 (en) * 1998-08-18 2005-01-25 The Regents Of The University Of California Preventing airway mucus production by administration of EGF-R antagonists
US7354894B2 (en) * 1998-08-18 2008-04-08 The Regents Of The University Of California Preventing airway mucus production by administration of EGF-R antagonists
TR200100560T2 (en) * 1998-08-18 2002-05-21 The Regents Of The University Of California Prevention of mucus production in the airway by administration of EGF-R Antagonists
KR100838617B1 (en) 1999-02-10 2008-06-16 아스트라제네카 아베 Quinazoline derivatives as angiogenesis inhibitors
DZ3223A1 (en) * 1999-10-19 2001-04-26 Merck & Co Inc TYROSINE KINASES INHIBITORS
US6403581B1 (en) * 2000-01-19 2002-06-11 American Cyanamid Company Method of inhibition of farnesyl-protein transferase using substituted benz (cd) indol-2-imine and-amine derivatives
US6420382B2 (en) * 2000-02-25 2002-07-16 Merck & Co., Inc. Tyrosine kinase inhibitors
US7030123B2 (en) 2000-05-31 2006-04-18 Astrazeneca Ab Indole derivatives with vascular damaging activity
US20020041880A1 (en) * 2000-07-05 2002-04-11 Defeo-Jones Deborah Method of treating cancer
AR030357A1 (en) 2000-08-18 2003-08-20 Lundbeck & Co As H DERIVATIVES 4 -, 5 -, 6 - AND 7-INDOL
ES2334641T3 (en) 2000-09-01 2010-03-15 Novartis Vaccines And Diagnostics, Inc. AZA HETEROCICLIC DERIVATIVES AND THERAPEUTIC USE.
US20030028018A1 (en) * 2000-09-11 2003-02-06 Chiron Coporation Quinolinone derivatives
BRPI0113757B8 (en) 2000-09-11 2017-11-07 Chiron Corp quinolinone derivatives as tyrosine kinase inhibitors
ES2247187T3 (en) * 2000-10-17 2006-03-01 MERCK & CO., INC. ORALALLY ACTIVE SALTS CONNECTIVITY TYROSINE KINASE.
US20020198252A1 (en) * 2001-05-24 2002-12-26 Joseph Payack Process for the preparation of alkylamine substituted indoles
US7102026B2 (en) * 2001-06-13 2006-09-05 Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság Process for preparing and isolating rac-bicalutamide and its intermediates
WO2002100339A2 (en) * 2001-06-13 2002-12-19 Biogal Gyogyszergyar Rt. Novel process for preparing rac-bicalutamide and its intermediates
US7642278B2 (en) 2001-07-03 2010-01-05 Novartis Vaccines And Diagnostics, Inc. Indazole benzimidazole compounds
DE10134196B4 (en) * 2001-07-13 2005-08-18 Forschungszentrum Karlsruhe Gmbh Technik Und Umwelt A pharmaceutical composition for inhibiting the uncontrolled proliferation and / or induction of cell apoptosis
US6872715B2 (en) 2001-08-06 2005-03-29 Kosan Biosciences, Inc. Benzoquinone ansamycins
US6927293B2 (en) * 2001-08-30 2005-08-09 Merck & Co., Inc. Tyrosine kinase inhibitors
AU2002323406A1 (en) * 2001-08-30 2003-03-18 Merck And Co., Inc. Tyrosine kinase inhibitors
US7101884B2 (en) * 2001-09-14 2006-09-05 Merck & Co., Inc. Tyrosine kinase inhibitors
AU2002361577A1 (en) * 2001-10-30 2003-05-12 Merck And Co., Inc. Tyrosine kinase inhibitors
EA200400680A1 (en) * 2001-12-12 2005-06-30 Пфайзер Продактс Инк. HINAZOLINA DERIVATIVES FOR THE TREATMENT OF ANOMALOUS GROWTH OF CELLS
CA2473572C (en) 2002-02-01 2011-05-10 Astrazeneca Ab Quinazoline compounds
US6822097B1 (en) 2002-02-07 2004-11-23 Amgen, Inc. Compounds and methods of uses
ATE326970T1 (en) * 2002-02-22 2006-06-15 Us Gov Veterans Affairs USE OF 4-(4-METHYLPIPERAZINE-1-YLMETHYL)-N 4-METHYL-3-(4-PYRIDINE-3-YL) PYRIMIDINE-2-YLAMINO) PHENYL BENZAMIDE FOR THE TREATMENT OF SEMINOMAS
US20060128720A1 (en) * 2002-03-21 2006-06-15 Kufe Donald W Inhibition of cell death responses induced by oxidative stress
GB0207362D0 (en) * 2002-03-28 2002-05-08 Univ Liverpool Chemotherapy
JP2005532280A (en) 2002-04-03 2005-10-27 アストラゼネカ アクチボラグ Compound
CA2480325A1 (en) * 2002-04-16 2003-10-30 Merck & Co., Inc. Solid forms of salts with tyrosine kinase activity
US6770660B2 (en) * 2002-05-06 2004-08-03 Artery Llc Method for inhibiting platelet aggregation
AU2003261354A1 (en) * 2002-08-02 2004-02-23 The Regents Of The University Of California New uses for inhibitors of inosine monophosphate dehydrogenase
US7825132B2 (en) * 2002-08-23 2010-11-02 Novartis Vaccines And Diagnostics, Inc. Inhibition of FGFR3 and treatment of multiple myeloma
EP1539754A4 (en) 2002-08-23 2009-02-25 Novartis Vaccines & Diagnostic Benzimidazole quinolinones and uses thereof
US20050256157A1 (en) * 2002-08-23 2005-11-17 Chiron Corporation Combination therapy with CHK1 inhibitors
AU2003290699B2 (en) * 2002-11-13 2009-08-27 Novartis Vaccines And Diagnostics, Inc. Methods of treating cancer and related methods
AU2003284572A1 (en) * 2002-11-22 2004-06-18 Yamanouchi Pharmaceutical Co., Ltd. 2-oxoindoline derivatives
EP1610614A2 (en) * 2003-03-27 2006-01-04 Merck & Co. Inc. Formulations for tyrosine kinase inhibitors
WO2004089930A1 (en) * 2003-04-02 2004-10-21 Imclone Systems Incorporated 4-fluoroquinolone derivatives and their use as kinase inhibitors
US20050043233A1 (en) * 2003-04-29 2005-02-24 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
ES2467160T3 (en) * 2003-05-19 2014-06-12 Irm Llc Immunosuppressive compounds and compositions
US20050020556A1 (en) * 2003-05-30 2005-01-27 Kosan Biosciences, Inc. Method for treating diseases using HSP90-inhibiting agents in combination with platinum coordination complexes
US7691838B2 (en) * 2003-05-30 2010-04-06 Kosan Biosciences Incorporated Method for treating diseases using HSP90-inhibiting agents in combination with antimitotics
US20050026893A1 (en) * 2003-05-30 2005-02-03 Kosan Biosciences, Inc. Method for treating diseases using HSP90-inhibiting agents in combination with immunosuppressants
US20050054589A1 (en) * 2003-05-30 2005-03-10 Kosan Biosciences, Inc. Method for treating diseases using HSP90-inhibiting agents in combination with antibiotics
US20050054625A1 (en) * 2003-05-30 2005-03-10 Kosan Biosciences, Inc. Method for treating diseases using HSP90-inhibiting agents in combination with nuclear export inhibitors
US20050020534A1 (en) * 2003-05-30 2005-01-27 Kosan Biosciences, Inc. Method for treating diseases using HSP90-inhibiting agents in combination with antimetabolites
US20050020557A1 (en) * 2003-05-30 2005-01-27 Kosan Biosciences, Inc. Method for treating diseases using HSP90-inhibiting agents in combination with enzyme inhibitors
JP2006526654A (en) * 2003-06-05 2006-11-24 メルク　エンド　カムパニー　インコーポレーテッド Substituted indoles and methods for preparing substituted indoles
WO2005014825A2 (en) 2003-08-08 2005-02-17 Arriva Pharmaceuticals, Inc. Methods of protein production in yeast
CA2544492C (en) 2003-11-07 2013-01-29 Chiron Corporation Pharmaceutically acceptable salts of quinolinone compounds having improved pharmaceutical properties
WO2005053692A1 (en) * 2003-12-01 2005-06-16 The Scripps Research Institute Advanced quinolinone based protein kinase inhibitors
GB0330002D0 (en) 2003-12-24 2004-01-28 Astrazeneca Ab Quinazoline derivatives
WO2005072766A2 (en) * 2004-01-27 2005-08-11 Boys Town National Research Hospital Peptides that bind to hsp90 proteins
BRPI0507891A (en) * 2004-02-20 2007-07-24 Chiron Corp modulation of inflammatory and metastatic processes
AU2005221151A1 (en) 2004-03-09 2005-09-22 Arriva Pharmaceuticals, Inc. Treatment of chronic obstructive pulmonary disease by low dose inhalation of protease inhibitor
CN1984663A (en) 2004-03-29 2007-06-20 南佛罗里达大学 Effective treatment of tumors and cancer with triciribine and related compounds
US20100009928A1 (en) 2004-03-29 2010-01-14 Cheng Jin Q Compositions including triciribine and taxanes and methods of use thereof
US20100009929A1 (en) 2004-03-29 2010-01-14 Cheng Jin Q Compositions including triciribine and bortezomib and derivatives thereof and methods of use thereof
US20110008327A1 (en) 2004-03-29 2011-01-13 Cheng Jin Q Compositions including triciribine and epidermal growth factor receptor inhibitor compounds or salts thereof and methods of use thereof
US20110223154A1 (en) * 2008-05-12 2011-09-15 University Of South Florida Compositions including triciribine and methods of use thereof
US20100028339A1 (en) 2004-03-29 2010-02-04 Cheng Jin Q Compositions including triciribine and trastuzumab and methods of use thereof
US20100173864A1 (en) 2004-03-29 2010-07-08 Cheng Jin Q Compositions including triciribine and one or more platinum compounds and methods of use thereof
EP1598348A1 (en) * 2004-05-18 2005-11-23 Aventis Pharma Deutschland GmbH Novel pyridazinone derivatives as inhibitors of CDK2
GB0420722D0 (en) * 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
US20080096859A1 (en) * 2004-10-01 2008-04-24 Sullivan Kathleen A Compositions and Methods for Treating Ophthalmic Diseases
EP2301546B1 (en) * 2005-01-27 2014-09-10 Novartis AG Treatment of metastasized tumors
US20080280902A1 (en) * 2005-01-28 2008-11-13 Fraley Mark E Inhibitors of Checkpoint Kinases
EP1883403A4 (en) * 2005-04-29 2011-02-16 Univ Ohio State Res Found Keratinocyte growth factor receptor - tyrosine specific inhibitors for the prevention of cancer metastatis
PT1885187E (en) 2005-05-13 2013-12-16 Novartis Ag Methods for treating drug resistant cancer
WO2006125130A1 (en) 2005-05-17 2006-11-23 Novartis Ag Methods for synthesizing heterocyclic compounds
KR101368519B1 (en) * 2005-05-23 2014-02-27 노파르티스 아게 Crystalline and other forms of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1h-benzimidazol-2-yl]-1h-quinolin-2-one lactic acid salts
WO2007058482A1 (en) * 2005-11-16 2007-05-24 Lg Life Sciences, Ltd. Novel inhibitors of protein kinase
US8658633B2 (en) * 2006-02-16 2014-02-25 Massachusetts Eye And Ear Infirmary Methods and compositions for treating conditions of the eye
AR059898A1 (en) 2006-03-15 2008-05-07 Janssen Pharmaceutica Nv DERIVATIVES OF 3-CIANO-PIRIDONA 1,4-DISUSTITUTED AND ITS USE AS ALLOSTERIC MODULATORS OF MGLUR2 RECEIVERS
TW200812615A (en) * 2006-03-22 2008-03-16 Hoffmann La Roche Tumor therapy with an antibody for vascular endothelial growth factor and an antibody for human epithelial growth factor receptor type 2
CA2655997A1 (en) 2006-06-30 2008-01-10 Schering Corporation Igfbp2 biomarker
US8246966B2 (en) * 2006-08-07 2012-08-21 University Of Georgia Research Foundation, Inc. Trypanosome microsome system and uses thereof
CA2669531A1 (en) * 2006-11-22 2008-06-05 University Of Georgia Research Foundation, Inc. Tyrosine kinase inhibitors as anti-kinetolastid and anti-apicomplexan agents
KR100799821B1 (en) * 2007-02-05 2008-01-31 동화약품공업주식회사 Novel imatinib camsylate and method for preparing thereof
TW200845978A (en) 2007-03-07 2008-12-01 Janssen Pharmaceutica Nv 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives
TW200900065A (en) 2007-03-07 2009-01-01 Janssen Pharmaceutica Nv 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives
CA2697399C (en) 2007-09-14 2016-01-19 Ortho-Mcneil-Janssen Pharmaceuticals, Inc. 1,3-disubstituted 4-(aryl-x-phenyl)-1h-pyridin-2-ones
RS51660B (en) 2007-09-14 2011-10-31 Ortho-Mcneil-Janssen Pharmaceuticals Inc. 1`,3`-disubstituted-4-phenyl-3,4,5,6-tetrahydro-2h, 1`h-[1,4`] bipyridinyl-2`-ones
US8216571B2 (en) 2007-10-22 2012-07-10 Schering Corporation Fully human anti-VEGF antibodies and methods of using
JP2012501298A (en) * 2008-05-12 2012-01-19 ユニヴァーシティ オブ サウス フロリダ Trisiribine-containing composition and method of using the same
PE20100851A1 (en) * 2008-06-24 2011-01-31 Hoffmann La Roche PYRIDIN-2-ONAS AND PYRIDAZIN-3-ONAS SUBSTITUTED AS Btk INHIBITORS
WO2010025890A1 (en) 2008-09-02 2010-03-11 Ortho-Mcneil-Janssen Pharmaceuticals, Inc 3-azabicyclo[3.1.0]hexyl derivatives as modulators of metabotropic glutamate receptors
US8691813B2 (en) 2008-11-28 2014-04-08 Janssen Pharmaceuticals, Inc. Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors
CA2756870A1 (en) 2009-03-31 2010-10-07 Arqule, Inc. Substituted indolo-pyridinone compounds
TWI410418B (en) 2009-04-29 2013-10-01 Ind Tech Res Inst Azaazulene compound, pharmaceutical composition, and method of inhibiting the activity of protein kinsae in a cell
MY153913A (en) 2009-05-12 2015-04-15 Janssen Pharmaceuticals Inc 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
EP2430031B1 (en) 2009-05-12 2013-04-17 Janssen Pharmaceuticals, Inc. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
EP2430022B1 (en) 2009-05-12 2013-11-20 Janssen Pharmaceuticals, Inc. 1,2,4-Triazolo[4,3-a]pyridine derivatives and their use for the treatment or prevention of neurological and psychiatric disorders
DK2769737T3 (en) 2009-07-20 2017-07-24 Bristol Myers Squibb Co COMBINATION OF ANTI-CTLA4 ANTIBODY WITH ETOPOSIDE FOR SYNERGISTIC TREATMENT OF PROLIFERATIVE DISEASES
AU2010310746B2 (en) 2009-10-20 2015-07-23 Nestec S.A. Proximity-mediated assays for detecting oncogenic fusion proteins
KR100953511B1 (en) * 2009-12-28 2010-04-21 (주)지노믹트리 Diagnosis Kit and Chip for Psoriasis
WO2011133687A2 (en) * 2010-04-20 2011-10-27 President And Fellows Of Harvard College Methods and compositions for inhibition of beta2-adrenergic receptor degradation
AU2011328203B2 (en) 2010-11-08 2015-03-19 Janssen Pharmaceuticals, Inc. 1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors
EP2643320B1 (en) 2010-11-08 2015-03-04 Janssen Pharmaceuticals, Inc. 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
WO2012062750A1 (en) 2010-11-08 2012-05-18 Janssen Pharmaceuticals, Inc. 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
RU2578848C2 (en) 2011-02-17 2016-03-27 Нестек С.А. Device and method for leukocyte and cancer cell recovery by filtration
CA2871711A1 (en) 2012-05-04 2013-11-07 Pfizer Inc. Prostate-associated antigens and vaccine-based immunotherapy regimens
JP2015524400A (en) 2012-07-19 2015-08-24 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Fumarate salt of 9- [4- (3-chloro-2-fluoro-phenylamino) -7-methoxy-quinazolin-6-yloxy] -1,4-diaza-spiro [5.5] undecan-5-one , Its use and preparation as drugs
AU2014205483B2 (en) 2013-01-10 2017-11-30 Gilead Sciences, Inc. Non-selective kinase inhibitors
JO3368B1 (en) 2013-06-04 2019-03-13 Janssen Pharmaceutica Nv 6,7-DIHYDROPYRAZOLO[1,5-a]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
MX371455B (en) 2013-08-02 2020-01-28 Pfizer Anti-cxcr4 antibodies and antibody-drug conjugates.
JO3367B1 (en) 2013-09-06 2019-03-13 Janssen Pharmaceutica Nv 1,2,4-TRIAZOLO[4,3-a]PYRIDINE COMPOUNDS AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
AU2014331796B2 (en) 2013-10-11 2020-05-07 Gilead Sciences, Inc. Spray dry formulations
KR20220038826A (en) 2014-01-21 2022-03-29 얀센 파마슈티카 엔.브이. Combinations comprising positive allosteric modulators or orthosteric agonists of metabotropic glutamatergic receptor subtype 2 and their use
LT3431106T (en) 2014-01-21 2021-02-10 Janssen Pharmaceutica Nv Combinations comprising positive allosteric modulators of metabotropic glutamatergic receptor subtype 2 and their use
US9388239B2 (en) 2014-05-01 2016-07-12 Consejo Nacional De Investigation Cientifica Anti-human VEGF antibodies with unusually strong binding affinity to human VEGF-A and cross reactivity to human VEGF-B
ES2708030T3 (en) 2014-10-20 2019-04-08 Inst Nat Sante Rech Med Methods to explore an individual in search of a cancer
ES2764299T3 (en) 2014-12-09 2020-06-02 Inst Nat Sante Rech Med Human monoclonal antibodies against AXL
WO2016135041A1 (en) 2015-02-26 2016-09-01 INSERM (Institut National de la Santé et de la Recherche Médicale) Fusion proteins and antibodies comprising thereof for promoting apoptosis
JP2018525029A (en) 2015-07-07 2018-09-06 インセルム（インスティチュート ナショナル デ ラ サンテ エ デ ラ リシェルシェ メディカル） Antibody having specificity for myosin 18A and use thereof
WO2017032867A1 (en) 2015-08-27 2017-03-02 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting the survival time of patients suffering from a lung cancer
WO2017055327A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of endothelial cells in a tissue sample
WO2017055326A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of myeloid dendritic cells in a tissue sample
WO2017055322A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of neutrophils in a tissue sample
WO2017055324A1 (en) 2015-09-29 2017-04-06 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of cells of monocytic origin in a tissue sample
MX2018010295A (en) 2016-02-26 2019-06-06 Inst Nat Sante Rech Med Antibodies having specificity for btla and uses thereof.
CA3025057A1 (en) 2016-05-25 2017-11-30 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and compositions for treating cancers
WO2018011166A2 (en) 2016-07-12 2018-01-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for quantifying the population of myeloid dendritic cells in a tissue sample
US11186634B2 (en) 2016-07-29 2021-11-30 INSERM (Institut National de la Santé et de la Recherche Médicale) Antibodies targeting tumor associated macrophages and uses thereof
US11365257B2 (en) 2016-10-21 2022-06-21 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods for promoting t cells response by administering an antagonist of human c-type lectin-like receptor 1 (CLEC-1)
WO2018081567A1 (en) 2016-10-27 2018-05-03 Pulmokine, Inc. Combination therapy for treating pulmonary hypertension
US20190345500A1 (en) 2016-11-14 2019-11-14 |Nserm (Institut National De La Santé Et De La Recherche Médicale) Methods and pharmaceutical compositions for modulating stem cells proliferation or differentiation
EP3589654A1 (en) 2017-03-02 2020-01-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Antibodies having specificity to nectin-4 and uses thereof
WO2018185516A1 (en) 2017-04-05 2018-10-11 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cardiovascular toxicity induced by anti-cancer therapy
WO2018189403A1 (en) 2017-04-14 2018-10-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment of cancer
JP7323457B2 (en) 2017-05-18 2023-08-08 アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル Methods and pharmaceutical compositions for the treatment of mast cell disease
WO2019072888A1 (en) 2017-10-11 2019-04-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting hepatocellular carcinoma treatment response
WO2019072885A1 (en) 2017-10-11 2019-04-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Magnetic nanoparticles for the treatment of cancer
US20210253593A1 (en) 2017-11-14 2021-08-19 Bristol-Myers Squibb Company Substituted indole compounds
CA3083158A1 (en) 2017-11-24 2019-05-31 Institut National De La Sante Et De La Recherche Medicale (Inserm) Methods and compositions for treating cancers
EP3720974A1 (en) 2017-12-07 2020-10-14 Institut National de la Sante et de la Recherche Medicale (INSERM) Method for screening a subject for a cancer
MX2020006093A (en) 2017-12-15 2020-08-24 Bristol Myers Squibb Co Substituted indole ether compounds.
BR112020011788A2 (en) 2017-12-19 2020-11-24 Bristol-Myers Squibb Company 6-azaindole compounds
MX2020005462A (en) * 2017-12-19 2020-09-07 Bristol Myers Squibb Co Substituted indole compounds useful as tlr inhibitors.
KR20200101398A (en) * 2017-12-19 2020-08-27 브리스톨-마이어스 스큅 컴퍼니 Amide substituted indole compounds useful as TLR inhibitors
KR20200101399A (en) 2017-12-20 2020-08-27 브리스톨-마이어스 스큅 컴퍼니 Amino indole compounds useful as TLR inhibitors
EA202091479A1 (en) 2017-12-20 2020-11-24 Бристол-Маерс Сквибб Компани ARYL- AND HETEROARYL-SUBSTITUTED INDOL COMPOUNDS
BR112020012002A2 (en) 2017-12-20 2020-11-17 Bristol-Myers Squibb Company diazaindole compounds
EP3775206A1 (en) 2018-03-28 2021-02-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cancer
US20210164984A1 (en) 2018-04-13 2021-06-03 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for predicting outcome and treatment of patients suffering from prostate cancer or breast cancer
WO2019211370A1 (en) 2018-05-03 2019-11-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cancer
WO2019211369A1 (en) 2018-05-03 2019-11-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treating cancer
US20210213020A1 (en) 2018-05-30 2021-07-15 Inserm (Institut National De La Santé Et De La Rechirche Médicale) Methods and pharmaceutical compositions for treating cancer
WO2019234221A1 (en) 2018-06-08 2019-12-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods for stratification and treatment of a patient suffering from chronic lymphocytic leukemia
WO2020030634A1 (en) 2018-08-06 2020-02-13 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and compositions for treating cancers
EP3849602A1 (en) 2018-09-10 2021-07-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Combination of her2/neu antibody with heme for treating cancer
PL3860998T3 (en) 2018-10-05 2024-06-17 Annapurna Bio Inc. Compounds and compositions for treating conditions associated with apj receptor activity
CN112912382B (en) 2018-10-24 2024-07-02 百时美施贵宝公司 Substituted indole dimer compounds
EP3924520A1 (en) 2019-02-13 2021-12-22 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and compositions for selecting a cancer treatment in a subject suffering from cancer
EP3935193A1 (en) 2019-03-06 2022-01-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Method to diagnose a cmmrd
JP2022538733A (en) 2019-05-20 2022-09-06 インセルム（インスティチュート ナショナル デ ラ サンテ エ デ ラ リシェルシェ メディカル） Novel anti-CD25 antibody
CN114144410A (en) 2019-07-19 2022-03-04 阿纳格纳斯生物技术股份有限公司 Polyarylurea derivatives and their use in the treatment of muscular diseases
US20220290244A1 (en) 2019-08-02 2022-09-15 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for screening a subject for a cancer
EP3800201A1 (en) 2019-10-01 2021-04-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Cd28h stimulation enhances nk cell killing activities
US20230040928A1 (en) 2019-12-09 2023-02-09 INSERM (Institut National de la Santé et de la Recherche Médicale) Antibodies having specificity to her4 and uses thereof
KR20230008751A (en) 2020-05-12 2023-01-16 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) Novel methods of treating cutaneous T-cell lymphoma and TFH derived lymphoma
WO2022101463A1 (en) 2020-11-16 2022-05-19 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of the last c-terminal residues m31/41 of zikv m ectodomain for triggering apoptotic cell death
EP4029501A1 (en) 2021-01-19 2022-07-20 Anagenesis Biotechnologies Combination of polyaromatic urea derivatives and glucocorticoid or hdac inhibitor for the treatment of diseases or conditions associated with muscle cells and/or satellite cells
JP2024508633A (en) 2021-01-29 2024-02-28 インセルム（インスティチュート ナショナル デ ラ サンテ エ デ ラ リシェルシェ メディカル） How to diagnose MSI cancer
US20220389104A1 (en) 2021-05-28 2022-12-08 Ose Immunotherapeutics Method for Treating CD127-Positive Cancers by Administering an Anti-CD127 Agent
WO2024052503A1 (en) 2022-09-08 2024-03-14 Institut National de la Santé et de la Recherche Médicale Antibodies having specificity to ltbp2 and uses thereof
WO2024061930A1 (en) 2022-09-22 2024-03-28 Institut National de la Santé et de la Recherche Médicale New method to treat and diagnose peripheral t-cell lymphoma (ptcl)
WO2024127053A1 (en) 2022-12-14 2024-06-20 INSERM (Institut National de la Santé et de la Recherche Médicale) Method to predict a response to immune checkpoint inhibitors in patient with msi cancer
WO2024161015A1 (en) 2023-02-03 2024-08-08 Institut National de la Santé et de la Recherche Médicale Method to treat age-related diseases

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU658646B2 (en) * 1991-05-10 1995-04-27 Rhone-Poulenc Rorer International (Holdings) Inc. Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase
US5578609A (en) * 1994-03-25 1996-11-26 The Dupont Merck Pharmaceutical Company 2-carbocyclic and 2-heterocyclic quinoline-4-carboxylic acids and salts thereof useful as immunosuppressive agents
GB9524104D0 (en) 1995-11-24 1996-01-24 Smithkline Beecham Spa Novel compounds
AU3071397A (en) 1996-05-20 1997-12-09 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
IL129825A0 (en) 1996-11-27 2000-02-29 Pfizer Fused bicyclic pyrimidine derivatives
CN1152031C (en) 1998-08-11 2004-06-02 诺瓦提斯公司 Isoquinoline derivatives with angiogenesis inhibiting activity
DZ3223A1 (en) * 1999-10-19 2001-04-26 Merck & Co Inc TYROSINE KINASES INHIBITORS

Also Published As

Publication number Publication date
BR0014843A (en) 2002-06-11
ZA200202985B (en) 2003-06-25
IS6326A (en) 2002-03-27
EP1226136A2 (en) 2002-07-31
KR20020038959A (en) 2002-05-24
JP2003512369A (en) 2003-04-02
EA200200473A1 (en) 2002-10-31
MY137656A (en) 2009-02-27
EE05107B1 (en) 2008-12-15
BG106710A (en) 2003-03-31
GEP20053530B (en) 2005-05-25
ATE286045T1 (en) 2005-01-15
ES2234698T3 (en) 2005-07-01
JP3822494B2 (en) 2006-09-20
NO20021820L (en) 2002-05-23
WO2001029025A3 (en) 2001-11-01
NZ518001A (en) 2004-05-28
CN1409708A (en) 2003-04-09
SK6912002A3 (en) 2003-08-05
EE200200201A (en) 2003-06-16
HUP0203323A2 (en) 2003-02-28
CA2387351A1 (en) 2001-04-26
WO2001029025A2 (en) 2001-04-26
RS50380B (en) 2009-11-10
TWI239957B (en) 2005-09-21
DE60017179D1 (en) 2005-02-03
JP2006206609A (en) 2006-08-10
PL354292A1 (en) 2003-12-29
CO5261601A1 (en) 2003-03-31
CA2387351C (en) 2009-09-08
SA06270148B1 (en) 2007-01-23
AU778588B2 (en) 2004-12-09
IS2165B (en) 2006-11-15
CN1213045C (en) 2005-08-03
AU1571001A (en) 2001-04-30
DE60017179T2 (en) 2006-01-05
IL148891A (en) 2008-12-29
EG24381A (en) 2009-04-05
YU28602A (en) 2004-12-31
NO20021820D0 (en) 2002-04-18
HK1054931A1 (en) 2003-12-19
KR100681724B1 (en) 2007-02-28
EA005812B1 (en) 2005-06-30
MXPA02003887A (en) 2002-09-30
HRP20020349A2 (en) 2004-02-29
EP1226136B1 (en) 2004-12-29
DZ3223A1 (en) 2001-04-26
US6306874B1 (en) 2001-10-23
CZ20021390A3 (en) 2002-09-11
PL202842B1 (en) 2009-07-31
TR200201051T2 (en) 2002-09-23
HUP0203323A3 (en) 2004-01-28
UA74560C2 (en) 2006-01-16
PT1226136E (en) 2005-04-29
SA01220048B1 (en) 2007-01-23
NO325696B1 (en) 2008-07-07
PE20010749A1 (en) 2001-07-16
BG65585B1 (en) 2009-01-30
SK286628B6 (en) 2009-02-05
IL148891A0 (en) 2002-09-12

Similar Documents

Publication Publication Date Title
AR035626A1 (en) INHIBITORS OF INHIBITORS OF THYROSINE KINASE, PHARMACEUTICAL COMPOSITION, PROCEDURE TO PREPARE IT, AND, USE OF THE COMPOUNDS IN THE PREPARATION OF MEDICINES
PE20230238A1 (en) KRAS G12C INHIBITORS
JP6527534B2 (en) Novel compounds as dual inhibitors of histone methyltransferase and DNA methyltransferase
PE20230249A1 (en) BICYCLIC HETEROARYL COMPOUNDS AND THEIR USES
AR119731A1 (en) NLRP3 INFLAMASOME INHIBITORS
RU2472797C2 (en) 2-[(2-(PHENYLAMINO)-1H-PYRROLO[2,3-d]PYRIMIDIN-4-YL)AMINO]BENZAMIDE DERIVATIVES AS IGF-IR INIBITORS FOR TREATING CANCER
AR058703A1 (en) THYROSINKINASE INHIBITING TRIAZOLOPIRIDAZINS, METHOD OF PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING THERAPEUTIC AND USES IN THE TREATMENT OF CANCER
AR102722A2 (en) A PIRAZOLO-QUINAZOLINE DERIVATIVE, ITS USE, A PROCEDURE TO PREPARE THEM, PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM, COMPOUNDS USED IN THEIR PREPARATION, A LIBRARY OF TWO OR MORE COMPOUNDS, AND A PRODUCT OR KIT
EA201991403A1 (en) TRANSMEMBRANE CONDUCTIVITY REGULATOR MODULATOR FOR MUKOVISCIDOSIS, PHARMACEUTICAL COMPOSITIONS, TREATMENT METHODS AND METHOD OF OBTAINING THE INDICATED MODULATOR
AR081058A1 (en) DERIVATIVES OF ARILMETOXI ISOINDOLINA, COMPOSITIONS THAT INCLUDE THEM AND THEIR USE IN THE TREATMENT OF CANCER.
PE20231312A1 (en) TRICYCLIC CARBOXAMIDE DERIVATIVES AS PRMT5 INHIBITORS
AR107714A1 (en) DERIVATIVES OF PIRAZOLO [1,5-A] PIRAZIN-4-ILO
AR064010A1 (en) AKT ACTIVITY INHIBITORS
ES2171884T3 (en) QUINAZOLINE COMPOUNDS.
AR040595A1 (en) DERIVATIVES OF REPLACED AMINA AND METHODS OF USE
AR104963A1 (en) DERIVATIVES OF 2- (PIRAZOLOPIRIDIN-3-IL) PYRIMIDINE AS JAK INHIBITORS
AR057380A1 (en) CHEMICAL COMPOUNDS DERIVED FROM 2-AZETIDINONE AND THERAPEUTIC USE OF THE SAME
AR123848A1 (en) SPIRO HETEROCYCLIC COMPOUNDS AND METHODS OF USE
RU2018126815A (en) Bicyclic hydroxamic acids useful as inhibitors of mammalian histone deacetylase activity
AR040644A1 (en) A BENZOXAZINE-2-TIONA PROGESTERONE RECEIVER MODULATORS, A PHARMACEUTICAL COMPOSITION, USE OF THE COMPOUND TO PREPARE A DEDICATION TO TREAT A NEOPLASIC-HORMONE-DEPENDENT DISEASE AND THE USE OF A BENZOXIONINE-2-BENZOYNAMINE-2-ILYNAMINE-2-TIONAZYNAMINE-2-TIONA-BENZOYNAMINE-2-TIONAIN OR BENZOXAZINA-2-ILIDEN
AR060619A1 (en) TRIAZOLOQUINAZOLINONAS AS INHIBITORS OF CONTROL POINT KINASES
AR120246A1 (en) HETEROARYL-BIPHENYL AMINES FOR THE TREATMENT OF PD-L1 DISEASES
AR063147A1 (en) INHIBITING NITROGEN HETEROCICLIC COMPOUNDS OF HISTAMINE H3 RECEPTORS, PREPARATION METHOD, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND USES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS.
AR057377A1 (en) CYCLOHEPTAPIRIDINE DERIVATIVES AS INHIBITORS OF TYROSINE KINASE. PHARMACEUTICAL COMPOSITIONS
PE20211456A1 (en) 7-SUBSTITUTED SULFONIMIDOYLPURINONE COMPOUNDS AND ITS DERIVATIVES FOR THE TREATMENT AND PREVENTION OF LIVER CANCER

Legal Events

Date Code Title Description
FB Suspension of granting procedure